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Stephen F Murphy, Jonathan F Anker, Daniel J Mazur, Christel Hall, Anthony J Schaeffer, Praveen Thumbikat
INTRODUCTION: Chronic pelvic pain syndrome (CPPS) is a complex disorder that affects a large proportion of all men. A limited understanding of its etiology and pathogenesis is reflected by the absence of effective therapies. Although CPPS is deemed clinically non-infectious with no well-defined etiological role for microbes, bacteria is readily isolated from both healthy and patient prostate secretion and urine samples. Our laboratory has previously demonstrated that a specific gram-negative bacterial isolate can induce CPPS-like symptoms in mice...
September 21, 2018: Prostate
Jiajia Wang, Zongliang Lu, Changpeng Wu, Yanwu Li, Ya Kong, Rui Zhou, Kun Shi, Jing Guo, Na Li, Jie Liu, Wei Song, He Wang, Mingxing Zhu, Hongxia Xu
BACKGROUND: Voltage-gated sodium channels (VGSCs) are involved in several cellular processes related to cancer cell growth and metastasis, including adhesion, proliferation, apoptosis, migration, and invasion. We here in investigated the effects of S0154 and S0161, two novel synthetic sodium channel blockers (SCBs), on human prostate cancer cells (PC3, DU145, and LnCaP) and a prostate cancer xenograft model. METHODS: The MTT assay was used to assess the anticancer effects of SCBs in PC3, DU145, and LnCaP cells...
September 21, 2018: Prostate
Domenica Roberto, Laurence H Klotz, Vasundara Venkateswaran
BACKGROUND: Cannabinoids have demonstrated anticarcinogenic properties in a variety of malignancies, including in prostate cancer. In the present study, we explored the anti-cancer effects of the synthetic cannabinoid WIN 55,212-2 (WIN) in prostate cancer. METHODS: Established prostate cancer cells (PC3, DU145, LNCaP) were treated with varying concentrations of WIN. Cell proliferation was determined by the MTS assay. The anti-migration and anti-invasive potential of WIN was examined by the wound healing assay and the matrigel invasion assay...
September 21, 2018: Prostate
Niall P Kelly, Hugh D Flood, David A Hoey, Patrick A Kiely, Subhasis K Giri, J Calvin Coffey, Michael T Walsh
BACKGROUND: Direct mechanical characterization of tissue is the application of engineering techniques to biological tissue to ascertain stiffness or elasticity, which can change in response to disease states. A number of papers have been published on the application of these techniques to prostate tissue with a range of results reported. There is a marked variability in the results depending on testing techniques and disease state of the prostate tissue. We aimed to clarify the utility of direct mechanical characterization of prostate tissue in identifying disease states...
September 17, 2018: Prostate
Jie Liu, Degang Ding, Zhaoqiang Jiang, Tao Du, Jianjun Liu, Zhaohui Kong
BACKGROUND: Macrophage polarization plays an important role in tumor microenvironment, which regulated the prognosis of prostate cancer. However, the potential role of it is still need further identification. METHODS: The M1 Macrophages were inducted using 100 ng/mL LPS and 100 ng/mL IFN-γ, the M1 Macrophages were inducted using 20 ng/mL IL-4. TAMs were obtained by culturing monocytes for 7 days in RPMI 1640 10% FBS with 50% of conditioned medium from PC-3 cells real-time PCR was performed to determine the expression of miR-148a, CCAT1, and PKCζ...
September 16, 2018: Prostate
Nassim Ghorbanmehr, Sedigheh Gharbi, Eberhard Korsching, Mahmood Tavallaei, Behzad Einollahi, Seyed Javad Mowla
BACKGROUND: Early detection of cancers improves patients' survival and decreases the treatment cost. Unfortunately, the current methods for diagnosis of bladder and prostate cancers, two most common urothelial malignancies, suffer from a low sensitivity and specificity. MicroRNAs, as a group of endogenously produced non-coding RNAs, regulate gene expression and their expression is observed to be altered in many cancers and cancer progression phenomena. The remarkable stability of microRNAs in biofluids and their unique expression pattern in different pathological conditions make them an appealing, noninvasive diagnostic method in cancer diagnosis...
September 7, 2018: Prostate
Zhixiong Chen, Qilong Jiang, Pingyu Zhu, Yanlin Chen, Xuemei Xie, Zhongbo Du, Li Jiang, Wei Tang
BACKGROUND: Nitrogen permease regulator-like 2 (NPRL2) is reported to be a tumor suppressor candidate gene and involved in the mTOR signaling and drug resistance in several cancers. However, the role of NPRL2 in regulating the resistance to Everolimus (EVS), an inhibitor of the mTOR, in castration-resistant prostate cancer (CRPC) is still unclear. Therefore, in present study, we evaluated the role of NPRL2 and its potential resistance to EVS in CRPC. METHODS: NPRL2 expression levels in prostate tissues, including benign prostate hyperplasia (BPH) tissues, primary prostate cancer (PCa) tissues, CRPC tissues, and several PCa cell lines (LNCaP, PC3, and enzalutamide-resistant LNCaP, named LNPER) were be evaluated by immunohistochemistry, RT-PCR, and Western blot...
September 3, 2018: Prostate
Yinan Li, Qingfu Zhang, Jessica Lovnicki, Ruiqi Chen, Ladan Fazli, Yuzhuo Wang, Martin Gleave, Jiaoti Huang, Xuesen Dong
Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of castrate-resistant prostate cancer characterized by poor patient outcome. Whole transcriptome sequencing analyses identified a NEPC-specific RNA splicing program that is predominantly controlled by the SRRM4 gene, suggesting that SRRM4 drives NEPC development. However, whether SRRM4 expression in patients may aid pathologists in diagnosing NEPC and predicting patient survival remains to be determined. In this study, we have applied RNA in situ hybridization and immunohistochemistry assays to measure the expressions of SRRM4, NEPC markers (SYP, CD56, and CHGA), and adenocarcinoma (AdPC) markers (AR, PSA) in a series of tissue microarrays constructed from castrate-resistant prostate tumors, treatment-naïve tumors collected from radical prostatectomy, and tumors treated with neoadjuvant hormonal therapy (NHT) for 0-12 months...
August 28, 2018: Prostate
Channing Paller, Hong Pu, Diane E Begemann, Cameron A Wade, Patrick J Hensley, Natasha Kyprianou
BACKGROUND: Prostate cancer progression is navigated by the androgen receptor (AR) and transforming-growth factor-β (TGF-β) signaling. We previously demonstrated that aberrant TGF-β signaling accelerates prostate tumor progression in a transgenic mouse model of prostate cancer via effects on epithelial-mesenchymal transition (EMT), driving castration-resistant prostate cancer (CRPC). METHODS: This study examined the antitumor effect of the combination of TGF-β receptor I (TβRI) inhibitor, galunisertib, and FDA-approved antiandrogen enzalutamide, in our pre-clinical model...
August 28, 2018: Prostate
Wanling Xie, Konrad H Stopsack, Sarah J Drouin, Henry Fu, Mark M Pomerantz, Lorelei A Mucci, Gwo-Shu M Lee, Philip W Kantoff
BACKGROUND: We previously identified a blood RNA transcript-based model consisting of six immune or inflammatory response genes (ABL2, SEMA4D, ITGAL, C1QA, TIMP1, and CDKN1A) that was prognostic for survival in cohorts of men with castration-resistant prostate cancer (CRPC). We investigated whether inherited variation in these six genes was associated with overall survival (OS) in men with CRPC. METHODS: The test cohort comprised 600 patients diagnosed with CRPC between 1996 and 2011 at Dana-Farber Cancer Institute...
August 23, 2018: Prostate
Stefania Tommasi, Brunella Pilato, Claudia Carella, Antonia Lasorella, Katia Danza, Ivan Vallini, Simona De Summa, Emanuele Naglieri
BACKGROUND: Castration resistant prostate cancer (CRPC) represents the most aggressive status of this neoplastic disease, also characterized by the absence of biomarkers predictive of clinical outcome. New drugs as abiraterone or enzalutamide, affecting androgen receptor pathway at different levels, inhibit the proliferative advantage of prostate cancer cells with important long term benefits. Despite the advantages of this second-generation androgen deprivation therapy (ADT), resistance mechanisms, primitive or acquired, often develop...
August 23, 2018: Prostate
Shaheen Alanee, Ahmed El-Zawahry, Danuta Dynda, Ali Dabaja, Kevin McVary, Mallory Karr, Andrea Braundmeier-Fleming
INTRODUCTION: There is accumulating evidence that variations in the human microbiota may promote disease states including cancer. Our goal was to examine the association between urinary and fecal microbial profiles and the diagnosis of prostate cancer (PC) in patients undergoing transrectal biopsy of the prostate. MATERIALS AND METHODS: We extracted total DNA from urine and fecal samples collected before a prostate biopsy performed for elevated prostatic specific antigen in patients suspected of having PC...
August 16, 2018: Prostate
Jillian S Weissenrieder, Jacqueline E Reilly, Jeffrey D Neighbors, Raymond J Hohl
BACKGROUND: Following androgen deprivation for the treatment of advanced adenocarcinoma of the prostate, tumors can progress to neuroendocrine prostate cancer (NEPC). This transdifferentiation process is poorly understood, but trafficking of transcriptional factors and/or cytoskeletal rearrangements may be involved. We observed the role of geranylgeranylation in this process by treatment with digeranyl bisphosphonate (DGBP), a selective inhibitor of geranylgeranyl pyrophosphate synthase which blocks the prenylation of small GTPases such as Rho and Rab family proteins, including Cdc42 and Rac1...
August 14, 2018: Prostate
Wenhua Huang, Xinya Su, Wei Yan, Zhe Kong, Dan Wang, Yan Huang, Qiaoli Zhai, Xiaowei Zhang, Hai Wu, Yao Li, Tao Li, Xuechao Wan
BACKGROUND: Prostate cancer (PCa) is a leading cause of death in males all over the world; besides, the diagnosis and therapy of it are still challenging. Researchers have revealed that long non-coding RNAs (lncRNAs) play important roles in the genesis and progression of human cancers, including PCa. METHODS: Bioinformatics analysis and Kaplan-Meier survival analysis were utilized to confirm TMPO-AS1 as a diagnostic and prognostic marker. The TMPO-AS1 levels in both patient tissues and PCa cell lines were determined by qRT-PCR analysis...
August 13, 2018: Prostate
Feilun Cui, Jianpeng Hu, Songyi Ning, Jian Tan, Huaming Tang
BACKGROUND: Prostate cancer (PCa) is one of the most malignant tumors of the male urogenital system. There is an urgent need to identify novel biomarkers for PCa. METHODS: In this study, we evaluated the expression levels of MCM10 in prostate cancer by analyzing public datasets (including The Cancer Genome Atlas and GSE21032). Furthermore, loss of function assays was performed to evaluate the effects of MCM10 on cell proliferation, apoptosis, and colony formation...
August 10, 2018: Prostate
Nikunj Gevariya, Marjorie Besançon, Karine Robitaille, Valérie Picard, Lamoussa Diabaté, Anwar Alesawi, Pierre Julien, Yves Fradet, Alain Bergeron, Vincent Fradet
BACKGROUND: Several lines of evidence suggest effects of dietary fat on prostate cancer (PCa) development and progression. Targeting omega (ω)-3:ω6 fatty acids (FA) ratio could be beneficial against PCa by favorably modulating inflammation. Here, we studied the effects of ω3- and ω6-enriched diets on prostate tumor growth and inflammatory response in androgen-deprived and non-deprived conditions. METHODS: Immune-competent eugonadal and castrated C57BL/6 mice were injected with TRAMP-C2 prostate tumor cells and daily fed with ω3- or ω6-enriched diet...
August 2, 2018: Prostate
Jonathan Olivier, Vasilis Stavrinides, Jonathan Kay, Alex Freeman, Hayley Pye, Zeba Ahmed, Lina Carmona Echeverria, Susan Heavey, Lucy A M Simmons, Abi Kanthabalan, Manit Arya, Tim Briggs, Dean Barratt, Susan C Charman, James Gelister, David Hawkes, Yipeng Hu, Charles Jameson, Neil McCartan, Shonit Punwani, Jan van der Muelen, Caroline Moore, Mark Emberton, Hashim U Ahmed, Hayley C Whitaker
INTRODUCTION: Diagnosing prostate cancer routinely involves tissue biopsy and increasingly image guided biopsy using multiparametric MRI (mpMRI). Excess tissue after diagnosis can be used for research to improve the diagnostic pathway and the vertical assembly of prostate needle biopsy cores into tissue microarrays (TMAs) allows the parallel immunohistochemical (IHC) validation of cancer biomarkers in routine diagnostic specimens. However, tissue within a biopsy core is often heterogeneous and cancer is not uniformly present, resulting in needle biopsy TMAs that suffer from highly variable cancer detection rates that complicate parallel biomarker validation...
August 2, 2018: Prostate
Nora M Navone, Wytske M van Weerden, Robert L Vessella, Elizabeth D Williams, Yuzhuo Wang, John T Isaacs, Holly M Nguyen, Zoran Culig, Gabri van der Pluijm, Cyril A Rentsch, Rute B Marques, Corrina M A de Ridder, Lukas Bubendorf, George N Thalmann, William Nathaniel Brennen, Frédéric R Santer, Patrizia L Moser, Peter Shepherd, Eleni Efstathiou, Hui Xue, Dong Lin, Jeroen Buijs, Tjalling Bosse, Anne Collins, Norman Maitland, Mark Buzza, Michelle Kouspou, Ariel Achtman, Renea A Taylor, Gail Risbridger, Eva Corey
BACKGROUND: While it has been challenging to establish prostate cancer patient-derived xenografts (PDXs), with a take rate of 10-40% and long latency time, multiple groups throughout the world have developed methods for the successful establishment of serially transplantable human prostate cancer PDXs using a variety of immune deficient mice. In 2014, the Movember Foundation launched a Global Action Plan 1 (GAP1) project to support an international collaborative prostate cancer PDX program involving eleven groups...
August 2, 2018: Prostate
Ping Chen, He Xiao, Wei Huang, De-Qiang Xu, Yu-Ming Guo, Xiao Wang, Xing-Huan Wang, Michael E DiSanto, Xin-Hua Zhang
BACKGROUND: Benign prostatic hyperplasia (BPH) is mainly caused by increased prostatic smooth muscle (SM) tone and prostatic volume. At the molecular level, SM myosin II (SMM II) and non-muscle myosin II (NMM II) mediate SM tone and cell proliferation while testosterone (T) plays a permissive role in the development of BPH. AIMS: The novel objective of this study was to elucidate the effects of T on the proliferation and apoptosis of rat prostatic cells and SM contractility as well as related regulatory signaling pathways...
August 2, 2018: Prostate
Balabhadrapatruni V S K Chakravarthi, Darshan S Chandrashekar, Sai Akshaya Hodigere Balasubramanya, Alyncia D Robinson, Shannon Carskadon, Uttam Rao, Jennifer Gordetsky, Upender Manne, George J Netto, Sunil Sudarshan, Nallasivam Palanisamy, Sooryanarayana Varambally
Prostate cancer (PCa) is one of the most frequently diagnosed cancers among men. Many molecular changes have been detailed during PCa progression. The gene encoding the transcription factor ERG shows recurrent rearrangement, resulting in the overexpression of ERG in the majority of prostate cancers. Overexpression of ERG plays a critical role in prostate oncogenesis and development of metastatic disease. Among the downstream effectors of ERG, Frizzled family member FZD4 has been shown to be a target of ERG...
July 26, 2018: Prostate
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